We propose to define the risk of disease recurrence or progression by clinical and histopathologic characteristics and molecular and genetic markers in a population-based study of women with ductal carcinoma in situ (DCIS) of the breast. Three study cohorts will be evaluated: (1) a population-based cohort of 1,744 women diagnosed with DCIS from 1983-96, identified by the Northern California Surveillance, Epidemiology, and End Results Program, who underwent lumpectomy alone for treatment, (2) women diagnosed with DCIS whose tissue has been collected at UCSF for the Breast Oncology Program database (N = 457), and (3) a subset of the 1,310 women initially diagnosed with DCIS who underwent lumpectomy and radiation therapy in the NSABPB-17 and NSABPB-24 trials. We will determine the risk of recurrence or progression of DCIS and/or invasive cancer in women treated by lumpectomy alone according to: (1) nuclear grade, necrosis type, margin width, and established molecular markers (p53, erbB-2, ER, PgR, and Ki67); (2) candidate molecular markers of cell cycle dysregulation (Cyclin D1, p16 methylation), tumor invasiveness (e.g., VEGF, factor VI11 related antigen, Cox-2), and stromal-breast epithelium interactions (e.g., uPA and related proteins, E-cadherin, beta 1integrin); and (3) a subset of chromosomal alterations detected by array-based comparative genomic hybridization. In addition, to validate out findings, we will evaluate women that underwent lumpectomy and radiation therapy to assess that the same measures that predict recurrence among women treated by lumpectomy alone also predict recurrence among women who received adjuvant radiotherapy (Group 3). The results of these studies will be used to develop a risk assessment tool based on measures that have been found to be independently associated with recurrence in a multivariate model. The risk assessment tool will estimate the risk of recurrence for an individual woman as a function of her clinical (e.g., age at diagnosis, menopause status) and histopathology (e.g., nuclear grade, margin width) information, established molecular markers (e.g., ER status, Ki67), and candidate markers.